IBD

Question 1

IBD definition

Answer 1

mucosal inflammatory conditions with chronic or recurring immune response and inflammation of the gastrointestinal (GI) tract

Question 2

two types of IBD

Answer 2

Ulcerative Colitis (UC): mucosal inflammation confined to rectum and colon
Crohn’s Disease (CD): transmural inflammation of GI tract that can affect any part from the mouth to the anus

Question 3

epidemiology of IBD

Answer 3

most prevalent in western countries
both sexes affected equally
peak incidence in second (CD) or third decade (UC)

Question 4

etiology of IBD

Answer 4

combination of immunologic, infectious, genetic, environmental factors - immune dysregulation, microflora of GI tract may trigger

Question 5

immunologic etiology of IBD

Answer 5

both autoimmune and non-autoimmune mechanisms
innate immune system involves intestinal barrier function, is associated with secretions in response to stimuli
gut wall infiltrated by WBCs - granuloma formation
cytokine disregulation

Question 6

microbial etiology of IBD

Answer 6

luminal microorganisms thought to be important in initiation of inflammation however no definitive infectious etiology
-shift toward more proinflammatory bacteria
-increased density of microflora
-potential loss of tolerance to normal GI flora
-bacterial antigens/ligands may induce and
propagate inflammation
-“microbiome” - ecological community of commensal, symbiotic, and pathogenic microorganisms

Question 7

genetic etiology in IBD

Answer 7

high concordance rate in monozygotic twins
first degree relatives have 20x risk of IBD
not a single gene phenomenon

Question 8

psychological etiology in IBD

Answer 8

stess may correlate with disease flares and impact QOL

Question 9

environmental etiology in IBD

Answer 9

“hygiene hypothesis”: cleaner conditions in developed countries expose patients to fewer pathogens/antigens at a young age - potentially altered immune response when encountered later in life
diet (potential association - causality unclear)
smoking - potentially protective in UC (reduced disease activity, fewer flares); associated with an increase frequency and severity of CD

Question 10

Drug related etiology of IBD

Answer 10

NSAIDs - may trigger disease occurrence or lead to flares, unclear whether COX-2 selective agents are associated with a decreased risk, generally avoid NSAIDs in pts with IBD
antibiotics - potential association, however causal relationship unclear

Question 11

UC pathophysiology

Answer 11

confined to rectum and colon and affects mucosal and submucosal layers (more superficial than CD)
-abscess formation in mucosal crypts, coalescence results in ulceration
extension and coalescence of ulcers may surround areas of normal tissue
mucosal damage and friability can result in substantial diarrhea and bleeding

Question 12

complications of UC

Answer 12

local, systemic and extraintestinal complications
local - hemorrhoids, anal fissures, perirectal abcesses
other major complications: colonic perforation (can be w/wo toxic megacolon), massive colonic hemorrhage, colonic stricture

Question 13

toxic megacolon

Answer 13

complication of UC - severe and potentially fatal
segmental or total colonic distention with acute colitis and signs of systemic toxicity
increase depth of ulceration
vasculitis and thrombosis
colonic dilation and potential perforation
associated with fever, tachycardia, abdominal distention, elevated WBCs

Question 14

colonic dysplasia/colorectal cancer (CRC)

Answer 14

risk of colonic dysplasia w transition to CRC is 5x greater in UC
cumulative risk of CRC is up to 20-30% at 30 years
screening colonoscopy with biopsies recommended at 8 years after UC onset and every 1-2 years after that

Question 15

CD pathophysiology

Answer 15

transmural inflammation
anywhere in GI tract (terminal ileum most common)
often discontinuous (normal bowel separating diseased bowel)
deep, elongated ulcers, cobblestone appearance
bowel wall injury may be extensive, associated with luminal narrowing

Question 16

complications of CD

Answer 16

small bowel stricture and obstruction possible
fistula common (20-40% lifetime risk) - fistula = pathologic connection between bowel and another tissue (skin, another segment of GI tract, bladder, or vagina)
less bleeding than UC (although anemia possible)
risk of carcinoma is increased, but not to the extent of UC
nutritional deficiencies common - weight loss, growth failure in children, iron deficiency anemia, vit B12 def., folate def., hypoalbuminemia, hypokalemia, osteomalacia

Question 17

extraintestinal manifestations of IBD

Answer 17

hepatobiliary - common (5-95% incidence) - hepatic: fatty liver, pericholangitis, autoimmune hepatits, cirrhosis; biliary - primary sclerosing cholangitis (PSC), cholangiocarcinoma, cholelithiasis
occular - iritis, uveitis, episcleritis, conjuctivits
bone and joint - arthritis: asymmetrical, migratory, typically involes one/few large joints and parallels disease activity; may be at increase risk for metabolic bone disease and osteoporosis (nutrient definiciences, inflammation, hypogonadism, use of CSs)
hematologic - anemia
coagulation - increase risk of VTE; higher during flares, consider prophylaxis if admitted for flare
dermatologic and mucocutaneous - variety of skin and mucosal lesions

Question 18

clinical presentation of UC

Answer 18

highly variable; may include intermittent illness and periods of remission
diagnosis made on clinical suspicion and confirmed by endoscopy (colonoscopy or sigmoidoscopy) and biopsy
disease extent (location of inflammation) determined by endoscopy

Question 19

signs and symptoms of UC

Answer 19

abdominal cramping
frequent BMs +/- blood +/- mucous (can range from frequent small volume to profuse diarrhea)
weight loss
paradoxical constipation possible
fever/tachycardia (esp. in severe disease)
extraintestinal: blurred vision/ocular signs; arthritis; dermatologic manifestations

Question 20

physical examination of UC

Answer 20

hemorrhoids, anal fissures, perirectal abscesses may be present
dermatologic/ocular findings

Question 21

lab tests for UC

Answer 21

decreased Hb/HCT
increased ESR/CRP
leukocytosis, hypoalbuminemia (severe dz)
(+) perinuclear antineutrophil cytoplasmicantibodies
fecal calprotectin and fecal lactoferrin

Question 22

types of UC

Answer 22

distal (left-sided): distal to splenic flexure

extensive: extending proximal to splenic flexure
proctitis: involving the rectal area
proctosigmoiditis: involving rectum and sigmoid colon
pancolitis: involving majority of colon

Question 23

UC disease classification

Answer 23

determined by s/sxs

1. Mild: under 4 stools/day (+/- blood); no systemic disturbance; normal ESR
2. Moderate: over 4 stools/day; minimal systemic disturbance
3. Severe: over 6 stools/day with blood; evidence of systemic disturbance (fever, tachycardia, anemia, or ESR over 30 mm/h)
4. Fulminant: over 10 stools/day with continuous bleeding; toxicity (severe systemic disturbances); abdominal tenderness; need for transfusion; colonic dilation

Question 24

clinical presentation of CD

Answer 24

highly variable, characterized by periods of remission and exacerbation
typical presentation includes diarrhea and abdominal pain - hematochezia in around 50% (less if no colonic involvement), should suspect diagnosis in children with impaired growth, esp. if associated w abdominal pain
diagnosis involves clinical evaluation in addition to endoscopic (upper and lower), laboratory, radiologic testing

Question 25

s/sxs of CD

Answer 25

``` malaise, fever abdominal pain frequent BMs hematochezia fistula weight loss/malnutrition arthritis ```

Question 26

PE of CD

Answer 26

abdominal mass/tenderness | perianal fissure, fistula

Question 27

laboratory tests with CD

Answer 27

Hb/HCT increased WBCs, ESR, CRP (+) anti-Saccharomyces cervisiae antibodies fecal calprotectin and fecal lactoferrin

Question 28

CD disease classification

Answer 28

no global classification system CDAI (crohn's disease activity index) - used to gauge response to therapy and determine remission treatment guidelines often use “clinical picture” mild-moderate: ambulatory with minimal other symptoms (dehydration, systemic toxicity, loss of body weight, abdominal tenderness), no obstruction moderate-severe: patients who fail therapy for mild-moderate disease, or those with fever, weight loss, abdominal pain/tenderness, vomiting, obstruction, anemia severe-fulminant: persistent symptoms or evidence of systemic toxicity despite corticosteroid or biologic treatment, or presence of cachexia, rebound tenderness, intestinal obstruction, or abscess

Question 29

IBD treatment overview

Answer 29

pharmacologic therapy, surgical therapy, nutrition support, treatment of complications, avoiding drugs that may exacerbate IBD goals of therapy: highly individualized; may include: -resolve acute inflammation/treatment of disease flare *resolve and/or prevent complications -maintain remission *alleviate extraintestinal manifestations -avoid need for surgical palliation/cure (patient priority) -surgical palliation/cure -maintain QOL inducing and maintaining remission** is an important ascept of therapy to improve outcomes and QOL and reduce complications - mucosal healing may be associated with better long term outcomes

Question 30

nonpharm therapy for IBD

Answer 30

nutrition support - no specific diet shown to be beneficial, address nutritional deficiencies, impaired absorption (enteral supplementation if necessary, parenteral nutrition - avoid unless absolutely necessary, supplement vitamin/mineral deficiencies), probiotic therapy surgery - resecting areas of inflammation, rates in UC may be around 5-30%, indications for surgery in CD are less established

Question 31

overview of pharm therapy in IBD

Answer 31

integral role, however no agents are curative ASAs (aminosalicylates) - sulfasalazine, mesalamine (5-ASA) corticosteroids (local and systemic) immunomodulators (immunosuppressives) - azathioprine, mercaptopurine (MP), cyclosporine, methotrexate biologics - anti-TNF-α agents (infliximab, adalimumab, certolizumab, golimumab); inhibitors of leukocyte adhesion/migration (natalizumab, vedolizumab) antimicrobials (metronidazole, ciprofloxacin)

Question 32

sulfasalazine

Answer 32

sulfapyridine (a sulfonamide) + 5-ASA (mesalamine) - cleaved by colonic bacteria to release sulfapyridine (absorbed and renally excreted) and 5-ASA (mainly remains in lumen, excreted in stool) - sulfapyridine is inactive, but associated with ADRs - 5-ASA is the active component, exerts actions locally - MOA may include anti-inflammatory effects, free radical scavenging

Question 33

mesalamine

Answer 33

can administer mesalamine alone -rapidly and completely absorbed in small intestine but not colon -formulation is important to deliver to affected area -topical (enemas): left-sided disease -suppository: proctitis -oral - delayed/controlled release generally topical is more effective than oral can use oral and topical together

Question 34

apriso

Answer 34

oral mesalamine agent 0.375 g in ER/DR capsule - dissolves at pH 6+ releases in colon* dosed once daily*

Question 35

lialda

Answer 35

oral mesalamine agent 1.2 g in ER/DR capsule - film dissolves at pH 6.8+ drug releases evenly throughout colon* dosed once daily*

Question 36

pentasa

Answer 36

oral mesalamine agent 250 mg or 500 mg in CR capsules releases in duodenum and ileum - up to 60% of dose reaches colon* dosed QID*

Question 37

asacol HD and delzicol

Answer 37

oral mesalamine agents 800 mg (asacol HD) or 400 mg (delzicol) in pH dependent coating - dissolves at pH 7+ releases in terminal ilium* dosed TID*

Question 38

olsalazine

Answer 38

``` dipentum oral mesalamine agent 250 mg dimer of 2 5-ASA molecules - mesalamine released after colonic bacteria cleaves bond release in colon dosed BID ```

Question 39

balsalazide

Answer 39

``` colazal oral mesalamine agent prodrug - released after colonic bacteria cleaves bond release in colon 750 mg tab dosed TID ```

Question 40

sulfasalazine ADRs

Answer 40

over 10% - NV, HA, anorexia, rash - initiate low dose, increase slowly over 1-2 weeks under 10%: anemia, hepatotoxicity, thrombocytopenia may be assocaited with hypersensitivity rxns in sulfa allergy monitpr CBC and LFTs at baseline, every other week for first 3 months, monthly for second 3 months, and periodically therafter, monitor BUN/SCr periodically drug interactions: antiplatelet/anticoagulant/NSAID - increased bleeding risk

Question 41

mesalamine ADRs

Answer 41

better tolerated than sulfasalazine common: NV, HA olsalazine: diarrhea less common: diarrhea, rash, constipation, anemia, abnormal LFTs, UC exacerbation drug interactions: antiplate/anticoag/NSAID - increased bleeding risk, agents affecting gastric pH - could influence release of drug in pH dependent dosage forms

Question 42

corticosteroids used in IBD

Answer 42

MOA: anti-inflammatory (note, unclear whether primary effect systemic or local) can be used parenterally (severe exacerbation/complication), orally, or rectally use for induction of remission, but not for maintenance Rectal Hydrocortisone (generally around 100-200 mg per day): -suppositories (Proctocort, Hemril), foam (Cortifoam), enema (Cortenema, Colocort) -note that systemic absorption is possible with rectal formulations

Question 43

budesonide in IBD

Answer 43

administered PO in CR formulation extensive first pass metabolism - minimal systemic exposure (9-21%) 6-8 mg/day for up to 8 weeks (possibly 16 wks) Enterocort EC: dosage form dissolves at pH > 5.5 (ileum), also available as enema Uceris: dosage covering dissolves at pH ≥ 7 (colon), polymer film provides extended release

Question 44

budesonide ADRs

Answer 44

possible similar to other glucocorticoids, however generally very well tolerated interactions: CYP3A inhibitors (ketoconazole, grapefruit juice, many others) - may increase systemic exposure by loss of high first pass

Question 45

systemic CSs in IBD

Answer 45

goal: remission and off steroid oral prednisone or prednisolone -40-60 mg/day -taper 5-10 mg/week until a dose of 20 mg/day is reached, then taper 2.5 mg/week intravenous methylprednisolone (16-20 mg q 6 h) or hydrocortisone (100 mg q 8 h) may be used for disease flares/induction of remission

Question 46

systemic CSs ADRs

Answer 46

-give calcium (1000-1500 mg/day) and vitamin D (800 U/day) while on steroids -may consider bisphosphonate tx in patients w risks for osteoporosis, pts using for > 3 months, recurrent users monitoring: see previous notes on corticosteroids -consider occasional bone mineral density scan (DEXA) in pts over 60, pts w risks for osteoporosis, pts using for over 3 months, recurrent users

Question 47

azathioprine (AZA) and mercaptopurine (MP, 6-MP)

Answer 47

can be effective in long term txt of UC and CD -generally reserved for pts who fail 5-ASA tx, and/or pts who are refractory to/dependent on steroids: can induce and maintain remission, steroid sparing, can use in conjunction w other drugs (5-ASAs, steroids, TNF-α antagonists), generally need to be used for extended periods* (weeks-months) before benefits observed AZA is a prodrug that is rapidly converted to 6-MP AZA: 0.5-1.5 mg/kg IBW, increase to a max of 2.5 mg/kg/d MP: 0.25-0.5 mg/kg IBW, increase to a max of 1.0- 1.5 mg/kg/d

Question 48

AZA and 6-MP ADRs and monitoring

Answer 48

GI: N/V/D, anorexia, stomatitis hematologic: bone marrow suppression (need TMPT genotype before initiation) hepatic: hepatotoxicity idiosyncratic: fever, rash, arthralgia, pancreatitis monitoring: baseline TPMT* CBC baseline and q week for 1st month, q 1-2 weeks after a dose change, q 1-3 months thereafter LFTs baseline and q 2 weeks until stable, then periodically

Question 49

cyclosporine in IBD

Answer 49

can be effective inducing remission in patients with refractory IBD (better data for UC) -not an option for long term use (i.e., use as “bridge therapy”) -generally reserved for pts who are refractory to/dependent on steroids: may delay colectomy, not for patients who have failed AZA or 6-MP, unclear whether it can be used following biologics -initial continuous IV infusion 2-4 mg/kg/day -PO conversion: double the IV dose, administered in divided doses q12h - taper over several weeks if response (up to several months)

Question 50

cyclosporine ADRs and monitoring

Answer 50

nephrotoxicity (does related) neurotoxicity metabolic (HTN, hyperlipidemia, hyperglycemia) other: GI upset, gingival hyperplasia, hirsutism monitor: BP baseline and q visit BUN/SCr baseline and q 2 weeks until stable, then periodically LFTs baseline q 2 weeks until stable, then periodically cya tr. conc goal ~200-400 ng/ml (t1/2 up to 24 h)

Question 51

cyclosporine drug interactions

Answer 51

substrate for CYP3A and P-glycoprotein - drugs/foods that can increase cyclosporine concentrations (not inclusive list): azole anti-fungals, macrolide antibiotics, calcium channel blockers, grapefruit and grapefruit juice - drugs that can decrease cyclosporine concentrations (not inclusive list): phenytoin, rifampin

Question 52

methotrexate

Answer 52

can be useful for treatment and maintenance of CD - may have steroid sparing effects, assist in inducing remission, allow steroid-tapering role in UC less defined 15-25 mg SC/IM q week

Question 53

methotrexate ADRs and monitoring

Answer 53

``` hematologic: bone marrow suppression (add folic acid 1 mg/day) GI: N/V/D, stomatitis, mucositis hepatic: cirrhosis, hepatitis, fibrosis (concern after 1.5 g in lifetime) pulm: hypersensitivity pneumonitis derm: rash, urticaria, alopecia teratogenic (contraception) monitoring: CXR baseline CBC baseline and q4-8 weeks SCr baseline and q4-8 weeks LFTs baseline and q4-8 weeks ```

Question 54

methotrexate contraindications

Answer 54

``` pregnancy pleural effusions chronic liver disease/EtOH abuse immunodeficiency preexisting blood dyscrasias leukopenia/t.cytopenia ClCr under 40 ml/min ```

Question 55

biologics overview

Answer 55

``` infliximab (Remicade) -anti-TNF- α antibody -CD and UC adalimumab (Humira) -anti-TNF- α antibody -CD and UC golimumab (Simponi) -human monoclonal antiTNF- α antibody -UC certolizumab pegol (Cimzia) -human pegylaged antiTNF- α Fab fragment -CD natalizumab (Tysabri) -anti-α-subunit of integrin's (prevents leukocyte adhesion/migration) -CD vedolizumab (Entyvio) -anti-α4β7 integrin antibody (α4β7 integrin is expressed on subset of T-lymphocytes) -UC and CD ```

Question 56

TNFa inhibitors ADRs

Answer 56

­ risk of serious infections (bacterial, viral, fungal) **avoid if active infection **tuberculin test (“PPD”), CXR, Hepatitis B/C prior to therapy -ensure vaccinations up to date **live vaccines contraindicated during tx and for 3 mo after injection site reactions - esp. with SC injection risk of malignancy (lymphoma) hepatosplenic T-cell lymphoma (HSTCL) risk (when combined with AZA) risk of demyelinating disease 0C/O in pts w history of cancer, demyelinating CNS disease, optic neuritis may exacerbate CHF (c/o in NYHA class III/IV)

Question 57

monitoring TNFa inhibitors

Answer 57

CXR, PPD at baseline S/S of infection (and patient self S/S of infection report) UA at baseline and q4-12 weeks CBC at baseline and q4-12 weeks SCr, lytes at baseline and q4-12 weeks LFTs at baseline and q4-12 weeks (possibly more frequent) Hep B, C inflammatory markers (e.g., Creactive protein)

Question 58

infliximab

Answer 58

UC and CD -mod - severe active CD and UC, steroid-dependent or fistulizing disease -induction and maintenance therapy IV infusion (2 hours*): 5 mg/kg at 0, 2 and 6 weeks, then 5-10 mg/kg q 8 weeks development of antibodies to infliximab (a.k.a., ATIs, ADAs) -decrease treatment response, potentially increase chance of infection -up to 10% of pts/year need to d/c infliximab -can escalate dose, decrease dosing interval -TDM (drug and antibodies) may be of value combining with immunosuppressives (e.g., azathioprine) may be of value** (and may ­risks of ADRs) hepatosplenic T-cell lymphoma (HSTCL) risk - increased­ if co-administered w azathioprine infusion-related reactions - acute or delayed additional monitoring: s/s of infection, vitals (each dose), infusion reactions (each dose), TDM (consider if treatment failure)

Question 59

adalimumab

Answer 59

UC and CD -mod - severe active CD and UC, steroid-dependent -can use for pts with poor response to infliximab -induction and maintenance therapy SQ injection: 160 mg at wk. 0, 80 mg at wk. 2, then 40 mg every second wk. -self-administration technique important** -in non-response/loss of response can increase dose to 80 mg q other wk. or 40 mg q wk. development of ADAs -human derived* (potentially less likely than infliximab) -measurement of antibodies possible

Question 60

golimumab

Answer 60

UC -mod - severe active UC, steroid-dependent -induction and maintenance therapy SQ injection: 200 mg at wk. 0, 100 mg at wk. 2, then 100 mg every 4 wks -self-administration technique important -no guidelines for dose escalation development of ADAs -human derived (potentially less likely than infliximab)

Question 61

certolizumab

Answer 61

CD -mod - severe active CD, steroid-dependent -induction and maintenance therapy SQ injection: 400 mg at wk. 0, 2, and 4, then 400 mg every 4 wks -self-administration technique important -no guidelines for dose escalation development of ADAs

Question 62

natalizumab

Answer 62

anti-α-subunit of integrin's (prevents leukocyte adhesion/migration) CD -inducing and maintaining remission -can use in pts who fail/don’t tolerate TNF-α inhibitors -NOT to be used in combination w immunosuppressant's, TNF-α inhibitors 300 mg IV q 4 wks -1 hour infusion -**d/c in patients w no benefit by 12 weeks and/or who are still steroid dependent within 6 months associated with progressive multifocal leukoencephalopathy (PML) -rare, lethal/disabling, untreatable CNS disorder related to opportunistic viral infection (JC virus) -available only through restricted distribution program -able to test for JC antibody -increased risk with: longer duration of therapy (over 2 years), prior immunosuppressant use, JC antibody positive -monitor closely for neurological events other ADRs similar to other biologics - can see hypersensitivity reactions, ADAs

Question 63

vedolizumab

Answer 63

anti-α4β7 integrin antibody (α4β7 integrin is expressed on subset of T-lymphocytes) UC and CD - inducing and maintaining remission, decreasing steroid dependence 300 mg IV at 0, 2, and 6 wks, then q 8 wks thereafter (infused over 30 min) ADRs similar to other biologics -can see hypersensitivity reactions, ADAs -PML not observed however close monitoring warranted due to similar MOA of natalizumab

Question 64

therapeutic drug monitoring (TDB) of biologics

Answer 64

loss of response - subtherapeutic level with no/low ADA - increase dose or decrease interval; consider adding immunomodulator therapeutic level - switch to vedolizumab with or without immunomodulator subtherapeutic level with high ADA - switch within class

Question 65

antimicrobials used in IBD

Answer 65

ciprofloxacin, metronidazole -can be used as adjunctive therapy in CD (and UC) in combination - may be of value in inducing remission -may be used in CD associated with fistulas/abscesses, perianal involvement rifamycin antibiotics also used ADRs: -agent specific ADRs -resistance -Clostridium difficile

Question 66

mild-moderate active UC

Answer 66

left-sided disease - within reach of enemas proctitis - within reach of suppositories extensive disease, pancolitis - requires systemic tx

Question 67

oral and/or topical ASAs for mild-mod active UC

Answer 67

oral and/or topical ASAs -if extensive disease - oral sulfasalazine or oral mesalamine derivative -if distal disease, topical mesalamine (enema or suppository) may be preferred -combo of oral and topical may be more effective for pts with left-sided/extensive disease if oral tx: -mesalamine derivatives better tolerated than sulfasalazine -sulfasalazine: 4-6 g/day in divided doses -mesalamine derivatives: 2.4-4.8 g/day -consider compliance, convenience, financial resources in product choice

Question 68

treatment for mild-mod active AC outside of ASAa

Answer 68

CR budesonide is alternative PO corticosteroids (prednisone 40-60 mg/day) may be used for patients refractory to ASAs AZA or 6-MP may be used for patients refractory to ASAs topical corticosteroids (foams, enemas, suppository) are effective for distal disease (ie, left sided, proctitis)

Question 69

moderate-severe active UC

Answer 69

systemic corticosteroids (PO prednisone 40-60 mg/day) consider TNF-α inhibitors in pts unresponsive to ASAs/other therapy, pts who are steroid dependent, pts who fail steroids infliximab + AZA may be superior to monotherapy

Question 70

severe-fulminant UC

Answer 70

require inpatient tx consider NPO (bowel rest) parenteral corticosteroids -methylprednisolone (16-20 mg q 6 h) or hydrocortisone (100 mg q 8 h) -generally treat 3-7 days (then transition to PO) consider TNF-α inhibitors or cyclosporine in pts unresponsive to IV steroids -cyclosporine: start IV, transition to PO, with transition to 6-MP or AZA - effective, but may delay rather than prevent colectomy infliximab - similar efficacy to cyclosporine

Question 71

UC: maintenance of remission

Answer 71

generally use an ASA, a TNF-α antagonist (infliximab and adalimumab), azathioprine, or 6-MP choice depends on part in the tx required to induce remission no role for corticosteroids ASAs -newer mesalamine derivatives better tolerated than sulfasalazine (2-2.4 g/day mesalamine equiv) -may use mesalamine enemas (if left-sided disease) or suppositories (if proctitis) -may use combination of topical/systemic (more effective than either alone) in pts who are steroid dependent or unresponsive to ASAs -azathioprine or 6-MP (slow to work: 3-6 months) - also consider as maintenance for pts who are transitioned to oral cyclosporine for induction of remission -TNF-α antagonist for pts who fail azathioprine or pts who required a TNF-α antagonist for induction of remission consider probiotic therapy

Question 72

mild-moderate active CD

Answer 72

sulfasalazine, newer mesalamine derivatives have minimal efficacy**, no longer recommended by some experts (controversial) -despite this, mesalamine derivatives frequently tried since well tolerated/familiar -consider formulation and site of action (e.g., Pentasa releases in small intestine) controlled release budesonide* -option for pts with ileal (distal) or right-sided disease antibiotics -e.g. metronidazole +/- ciprofloxacin -variable efficacy, possible option if perianal disease, unresponsive to sulfasalazine, generally not first line

Question 73

moderate-severe active CD

Answer 73

systemic corticosteroids (PO prednisone 40-60 mg/day) -tx until resolution of sx and resumption of wt gain hospitalized patients may receive IV corticosteroids -methylprednisolone (16-20 mg q 6 h) or hydrocortisone (100 mg q 8 h) immunomodulators (AZA and 6-MP) are not recommended to induce remission** (may help maintain remission after induced w steroids) -generally reserved for pts who are not responding to standard tx or who are steroid dependent MTX is alternative to AZA -induction and/or maintenance in steroid dependent/refractory TNF-α antagonists also effective -can use in patients failing immunosuppressive tx, steroid dependent pts -infliximab + AZA may be more effective than either alone adalimumab may be used - SC administration, possible option in pts who lose response to infliximab, others: certolizumab, natalizumab, vedolizumab

Question 74

severe-fulminant CD

Answer 74

require inpatient tx** consider NPO (bowel rest) parenteral corticosteroids (if no abscess) -methylprednisolone (16-20 mg q 6 h) or hydrocortisone (100 mg q 8 h) -generally treat 3-7 days (then transition to PO) consider cyclosporine (or tacrolimus) in pts unresponsive to IV steroids -limited data, start IV, transition to PO may consider infliximab (or other biologic) if not attempted prior

Question 75

CD maintenance of remission

Answer 75

minimal evidence sulfasalazine and PO mesalamine derivatives are effective -may try due to favorable adverse effect profile - mesalamine may have a role in preventing post-surgical relapse no role for systemic corticosteroids budesonide has minimal long-term efficacy limited data regarding antibiotics AZA and 6-MP are effective -esp. in steroid-induced or infliximab-induced remission -often consider first line MTX -alternative to AZA and 6-MP, esp. in pts w initial response to MTX TNF-α antagonists are options for CD maintenance -infliximab may be used with AZA or 6-MP -others: natalizumab, vedolizumab -clinical controversy: bottom-up or top-down approach